title: Tumor-targeting transferrin nanoparticles for systemic polymerized siRNA delivery in tumor-bearing mice.
abstract: Transferrin (TF) is widely used as a tumor-targeting ligand for the delivery of anticancer drugs because the TF receptor is overexpressed on the surface of various fast-growing cancer cells. In this article, we report on TF nanoparticles as an siRNA delivery carrier for in vivo tumor-specific gene silencing. To produce siRNA carrying TF nanoparticles (NPs), both TF and siRNA were chemically modified with sulfhydryl groups that can build up self-cross-linked siRNA-TF NPs. Self-polymerized 5'-end thiol-modified siRNA (poly siRNA, psi) and thiolated transferrin (tTF) were spontaneously cross-linked to form stable NPs (psi-tTF NPs) under optimized conditions, and they could be reversibly degraded to release functional monomeric siRNA molecules under reductive conditions. Receptor-mediated endocytosis of TF induced rapid tumor-cell-specific uptake of the psi-tTF NPs, and the internalized NPs resulted in a downregulation of the target protein in red-fluorescent-protein-expressing melanoma cancer cells (RFP/B16F10) with negligible cytotoxicity. After systemic administration, the psi-tTF NPs showed marked accumulation at the tumor, leading to successful target-gene silencing in vivo. This psi-tTF NP system provided a safe and effective strategy for in vivo systemic siRNA delivery for cancer therapy.
authors.affiliation: Center for Theragnosis, Korea Institute of Science and Technology , 39-1 Hawolgok-dong, Sungbuk-gu, Seoul 136-791, South Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Yhee
authors.forename: So Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sangmin
authors.initials: S
authors.lastname: Lee
authors.forename: Seungyong
authors.initials: S
authors.lastname: Song
authors.forename: Hyun Su
authors.initials: HS
authors.lastname: Min
authors.forename: Sun-Woong
authors.initials: SW
authors.lastname: Kang
authors.forename: Sejin
authors.initials: S
authors.lastname: Son
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis; D020868:Gene Silencing; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D058105:Polymerization; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014018:Tissue Distribution; D014168:Transferrin / Q000737:chemistry*
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D013438:Sulfhydryl Compounds; D014168:Transferrin